Process for preparation of 2-acetonyl-benzoxazoles and naphthoxazoles



United States Patent PROCESS FOR PREPARATION OF Z-ACETONYL- BENZOXAZOLESAND NAPHTHOXAZOLES Emil B. Ranch, Port Dickinson, and John A. Welsh,Bingharnton, N.Y., assignors to General Aniline 8: Film Corporation, NewYork, N.Y., a corporation of Delaware No Drawing. Filed Jan. 18, 1965,Ser. No. 426,425 9 Claims. (Cl. 260-307) This invention relates to aprocess of preparing 2-acetonyloXazoles which comprises reacting aZ-methyloxazole with an alkyl ester of an aliphatic carboxylic acid inan amide diluent using an alkali metal hydride catalyst.

In our copending application, Ser. No. 426,387, filed on even date ofthis application, we have disclosed a new method of preparingZ-phenacyloxazoles. The process comprises reacting a suitableZ-methyloxazole, such as 2- methylbenzoxazole, with an alkyl ester of anaromatic carboxylic acid, such as ethyl benzoate, in an inert diluent,such as an aromatic hydrocarbon, using an alkali metal hydride catalyst.Generally speaking the process disclosed in said copending applicationis not utilizable in the preparation of the compounds of this inventionsince the corresponding alkyl esters of aliphatic monocarboxylic acidshave a tendency to condense with themselves rather than with theZ-methyl group of the Z-methyloxazole compounds. This propensity towardsauto-condensation is particularly marked in the condensation of estersof acetic and propionic acids. This self-condensation is so prevalentwhen using an aromatic hydrocarbon diluent that essentially all of analkyl ester of acetic acid will condense with itself to form acetoaceticacid ester without any reaction of the Z-methyl group of the2-methyloxazole compound.

The object of this invention is to provide a new method of preparingZ-acetonyloxazoles. A further object of this invention is to provide amethod of preparing Z-acetonyl- 'benzoxazoles. We have now found that itis possible to condense alkyl esters of acids such as acetic acid,propionic acid, etc. with Z-methyloxazoles using a suitable alkali metalcatalyst hydride by carrying out said reaction in an amide diluent suchas dimethyl formamide. This is highly surprising since attempts to carryout the condensation of alkyl esters of aromatic monocarboxylic acidsunder the same conditions in a diluent of this type (dirncthylformamide) has resulted in lower yields of 2-phenacyloxazoles than whenan aromatic hydrocarbon diluent was employed. Whereas the condensationof an alkyl ester of a lower aliphatic monocarboxylic acid in anaromatic hydrocarbon diluent results in essentially completeautocondensation, yields as high as 30% of the desiredZ-acetonyloxazoles have been obtained by carrying out the reaction indirnethyl formamide.

The 2- acetonyloxazoles of this invention can be represented by theformula 0 /N 1'tCH -ii-CH -C \D wherein D is an ortho divalent arylenegroup, R is a group selected from the class consisting of hydrogen,halogen, alkyl of 1 to 16 carbon atoms and haloalkyl of 1 to 16 carbonatoms.

Briefly, the compounds of our invention can be prepared by reacting asuitable 2-methyloxazole with an alkylester of an aliphatic carboxylicacid having 2 to 18 carbon atoms in the acid moiety in an amide diluent,such as dimethyl formamide and dimethyl acetamide, using a catalyticamount of alkali metal hydride catalyst. The re- 3,3 16,2 74 PatentedApr. 25, 1967:

action is carried out at a temperature of about 20 to C. until theevolution of hydrogen from the decomposition of the alkali metal hydridehas ceased.

Suitable Z-methyloxazoles of the benzene and naphthalene seriesutilizable in our invention include Z-methylbenzoxazole,2,5,6-trimethylbenzoxazole, 2-methyl-5-ethylbenzoxazole,2-methyl-4-bromobenzoxazole, Z-methyl- 5-octylbenzoxazole,2-methyl-naphth(2.3) oxazole, 2- methyl-naphth(2.l) oxazole,2methyl-naphth( 1.2) oxazole, etc. Of these the commercially availableZ-methylbenzoxazole, 2,5,6-trimethylbenzoxazole and S-phenyl-Z-methylbenzoxazole are preferred since these compounds are commerciallyavailable and are desirable starting ma: terials for the preparation ofdyes useful in photographic emulsions. As used herein the terms a2-methylbenzoxazole, and a Z-methylnaphthoxazole include thecorresponding substituted and unsubstituted oxazoles containinginnocuous, non-reactive substituents on the arylene ring, such'as alkyl,halo (e.g. chloro or bromo), hydroxy, alkoxy (e.g. methoxy or ethoxy)which do not interfere with the claimed reaction. Accordingly compoundsbearing these groups are deemed to be equivalents of the unsubstitutedZ-methyloxazoles of the benzene and naphthalene series.

Suitable alkyl esters of aliphatic monocarboxylic acids useful in ourinvention include methyl acetate, ethyl acetate, ethyl propionate,chloroethyl acetate, ethyl p-chloropropionate, octyl butyrate, ethylstearate, etc. In general, the lower alkyl (methyl and ethyl) esters ofacetic acid and propionic acid are preferred. The alcohol moiety of theester is relatively unimportant since the alcohol portion does not endup in the final Z-acetonyloxazole compound. The esters of acetic andpropionic acids are preferred since these groupings result inZ-acetonyloxazole compounds which have the greatest utility insubsequent formation of dye intermediates. Esters of the highercarboxylic acids, such as the butyrate through stearate, are lesspreferred because of the bulky nature imparted to the ketonic chain ofthe Z-oxazole compounds.

Unfortunately the preferred aliphatic m'onocarboxylic acid esters havethe greatest tendency towards autocondensation. This tendency towardsautocondensation decreases as the chain length of the carboXylic acidmoiety increases. Accordingly, the yield of Z-acetonyloxazole compoundincreases as the chain length of aliphatic acid moiety increases. Thisis counterbalanced by the greater utility of the 2-acetonyloxazole basedon esters of acetic acid and propionic acid. In view of this tendency ofthe lower aliphatic acids to react with each other, it is desirable inorder to maximize yields of the desired product to employ at least onemole of the lower aliphatic monocarboxylic acids per mole ofZ-methyloxazole.

The catalysts utilizable in our invention comprise the alkali metalhydrides such as sodium hydride, potassium hydride, lithium hydride,rubidium hydride and cesium hydride. These catalysts can be used in aconcentration of about 0.5 to 5 moles per mole of Z-methyloxazole.Unlike our copending application where the yield of 2- phenacyloxazolesincreases as the concentration of the alkali metal hydride increasesfrom about 1 to 2 moles per mole of Z-methyloxazole, the yield of2-acetony1oxazoles does not appear to increase as the concentration ofcatalyst increases from 1 to 2 moles per mole of Z-methyloxazole.Accordingly, it is preferred from an economic point of view to use aboutone mole of alkali metal hydride catalyst per each mole ofZ-methyloxazole.

Diluents utilizable in our invention include the N,N- disubstitutedamides of lower fatty acids, such as N,N-dimethyl formamide andN,N-dimethyl acetamide.

The exothermic condensation can be carried out con- 'eniently attemperatures of about 20 to 120 C. or higher. ."he maximum tempeartureutilizable is generally dependnt upon the boiling point of the diluentin which the eaction is carried out. If desired, pressure apparatus andligher temperatures can be utilized. However no advanages have beenfound in such techniques.

As indicated above, the Z-acetonyloxazoles of this inention are valuabledye intermediates. These com- )OlllJdS have an active methylene groupwhich makes it ossible to condense them with fl-anilino-vinylazolium:alts to form merocyanine dyes.

The examples following are merely illustrative and :hould not beconstrued as limiting the scope of this inlention.

Example I This example illustrates the preparation of 2-acetonyl-)enzoxazole. One hundred and fifty ml. dry dimethyl formamide and 24 g.(0.5 M) of sodium hydride (50% )il dispersion) were placed in a cleandry l-liter flask equipped with stirrer, reflux condenser, nitrogeninlet and butlet tubes. There was added under nitrogen a solution at 66g. Z-methylbenzoxazole (0.5 M) in 100 ml. dry dimethyl formamide. Asolution of 44 g. ethyl acetate (0.5 M) in 150 ml. dry dimethylformamide was added dropwise over a thirty mintue period. The evolutionof hy- :lrogen was vigorous and the reaction rapidly reached atemperature of 58 C. where it was maintained by a cold water bath. Afterthe evolution of hydrogen ceased, the clear red solution was cooled to50 C. and added to 1500 ml. water. The aqueous composition was adjustedto pH 5 with glacial acetic acid. The brown oil layer was separated andthe aqueous layer was extracted with ether. The oil layer and etherextract were combined, dried with sodium sulfate, the ether evaporatedand the Z-acetonylbenzoxazole distilled at 124-134 C./2 mm. Twenty-oneand two-tenths grams of a yellow oily 2-acetonylbenzoxazole compositionwas stirred in pet ether to give 15.5 g. (20% of theoretical yield) of awhite crystalline solid melting at 7576 C.

, Analysis for C H NO Calc.: C, 68.55%; H, 5.18%; N, 7.99%. Found: C,68.68%, 68.63%;H, 5.17%, 5.09%; N, 7.73%, 7.94%.

Essentially the same results are obtained by replacing the ethyl acetatewith equivalent molar concentration of methyl acetate or propyl acetateor by replacing sodium hydride with an equivalent molar concentration ofpotassium hydride.

- The corresponding 2-(w-chloroacetonyl)-benzoxazole is obtained byusing 0.5 mole ethyl chloroacetate in place of ethyl acetate.

Example II This example illustrates the preparation of2-(w-methylacetonyl)-5,6 dimethylbenzoxazole. Fifty ml. dry dimethylformamide and 64 g. (0.133 M) sodium hydride (50% oil dispersion) wereplaced in a clean dry 500 ml. flask equipped with stirrer, refluxcondenser, nitrogen inlet and outlet tubes. There was added undernitrogen a solution of 21.4 g. 2,5,6-trirnethylbenzoxazole (0.133 M) in50 ml. dry dimethyl formamide. A solution of 13.6 g. ethyl propionate(0.133 M) in 35 ml. dry dimethyl formamide was added dropwise over athirty minute period. The evolution of hydrogen was vigorous andreaction rapidly reached a temperature of 6065 C., where it wasmaintained with alternate heating and cooling. After the evolution ofhydrogen ceased, the clear red solution was cooled to 50 C. and added to300 ml. water. The aqueous composition was adjusted to pH 5 with glacialacetic acid, cooled and stirred until the gummy solid2-(w-methylacetonyl)-5,G-dimethylbenzoxazole became filterable. Theproduct was filtered, washed with water and dried over calcium chloride.After one recrystallization from pet ether there was obtained 10 g. oflight yellow crystalline 2-(w-methylacetonyl)-5,6 dimethylbenzoxazole(35% of the theoretical yield) which melted at 81-83" C. After a secondrecrystallization the product melted at 84- 84.5 C.

Analysis for C H NO Calc.: C, 71.86%; H, 6.96%. Found: C, 71.85%,71.96%; H, 6.90%, 7.05%.

The corresponding 2-(w-heptadecylacetonyl)-5,6 dimethylbenzoxazole isobtained by using 0.133 mole ethyl stearate in place of ethylpropionate. The corresponding 2-(w-methylacetonyl)-naphth (1.2)oxazoleis obtained by using 0.133 mole 2-methylnaphth(1.2) oxazole in place of2,5,6-trimethylbenzoxazole.

Example III This example illustrates the preparation of 2-acetonyl-5,6-dimethylbenzoxazole. The process described in Example II wasemployed using a reaction temperature of 38-50 C. and the followingreactant compositions:

A. 4.8 g. (0.1 M) sodium hydride (50% oil dispersion) in 50 ml. dimethylformamide.

B. 1 6.1 g. 2,5,6-trimethylbenzoxazole (0.1 M) in 50 ml.

dimethyl formamide.

C. 8.8 g. ethyl acetate (0.1 M) in 40 ml. dimethyl formamide.

Example IV This example illustrates the preparation ofZ-(w-IIlGthYlacetonyl)-benzoxazole. The process described in Example Iwas employed using the following reactant compositions:

A. 24 g. (0.5 M) sodium hydride (50% oil dispersion) in ml. dimethylformamide.

B. 66.5 g. 2-rnethylbenzoxazole (0.5 M) in 120 ml. di-

methyl formamide.

C. 51 g. ethyl propionate (0.5 M) in ml. dimethyl formamide.

A brown oil was separated from the acidulated aqueous reaction mixture.The aqueous portion was extracted three times with 100 ml. portions ofchloroform. The chloroform extracts and brown oil were combined, driedwith sodium sulfate, the chloroform distilled off and the productdistilling at 138-l42 C./2 mm. was collected. The light yellow oildistillate which crystallized on cooling to 15 C., was dissolved in petether. On cooling to 5 C., 17 g. (20% of theoretical yield) of whitecrystalline 2-(w-methylacetonyl)-benzoxazole having a melting point of30-32 C. was obtained.

Analysis for C H O N: Calc.: C, 69.82%; H, 5.64%; N, 7.40%. Found: C,69.60%, 69.69%; H, 5.88%, 5.76%; N, 7.47%, 7.75%.

Essentially the same results are obtained using dimethyl acetamide asthe diluent.

Variations and modifications can be made in the procedures, compositionsand materials herein described without departing from the scope orspirit of this invention. In the claims that follow the term arylene isused in a generic sense to include substituted and unsubstituteddivalent aromatic groups and the terms phenylene and naphthalene areused to include unsubstituted and hydrocarbon substituted groups unlessother substituents are specifically recited.

We claim:

1. The process of preparing a 2-acetonyloxazo1e which comprises reactingan alkyl ester of an aliphatic carboXylic acid with a Z-methyloxazoleselected from the group consisting of 2-methy1benzoxazoles and 2-methy1napthoxazoles in the N,N-dimethylarnide of a lower fatty acid in thepresence of a catalytic amount of an alkali metal hydride catalyst.

2. The process of claim 1, wherein said amide comprises dimethylformamide.

3. The process of claim 1, wherein said amide comprises dimethylacetamide.

4. The process of claim 1, wherein said alkyl ester comprises an esterof acetic acid.

'5. The process of claim 1, wherein said alkyl ester comprises an esterof propionic acid.

6. The process of claim 1, wherein said Z-methyloxazole comprises2-methylbenzoxazole.

7. The process of claim 1, wherein said Z-methyloxazole comprises2,5,6-trimethylbenzoxazole.

8. The process of claim 1, wherein said Z-methyloxazole comprisesZ-methyl-S-phenylbenzoxazole.

9. The process of claim 1, wherein said reaction is carried out at from20-150 C.

No references cited. ALEX MAZEL, Primary Examiner. RICHARD J. GALLAGHER,Assistant Examiner.

1. THE PROCESS OF PREPARING A 2-ACETONYLOXAZOLE WHICH COMPRISES REACTINGAN ALKYL ESTER OF AN ALIPHATIC CARBOXYLIC ACID WITH A 2-METHYLOXAZOLESELECTED FROM THE GROUP CONSISTING OF 2-METHYLBENZOXAZOLES AND2-METHYLNAPTHOZAZOLES IN THE N,N-DIMETHYLAMIDE OF A LOWER FATTY ACID INTHE PRESENCE OF A CATALYTIC AMOUNT OF AN ALKALI METAL HYDRIDE CATALYST.